3-(2-Hydroxyethyl)-2-methylbenzothiazolium Bromide

1. Introduction

Very few papers in English were found in the literature that deal with the synthesis of 3-(2-hydroxyethyl)-2-methylbenzothiazolium bromide 3 or iodide [1,2]. The rest of the references found were in Chinese or Japanese [3,4,5] or related to the patent literature [6,7,8] and thus were relatively inaccessible. The preparation of 3 with a reaction time of less than 2 h has only been reported once, but in that reference the proposed method required special conditions and MW system [1]. 3-(2-Hydroxyeth-yl)-2-methylbenzothiazolium bromide is a useful compound. It has been shown that this derivative, which incorporates a benzothiazole subunit, exhibits very high static first hyperpolarizability values in the acido-generated form [2]. This compound is a typical intermediate for the preparation of cyanine dyes [1,2,8] which have different applications in the preparation of, for example, styryl dyes [2], or squaraine dyes [5,6]. The usual synthetic method requires heating for up to 18 h [8]. However, we have found that 3 can be obtained in a shorter time by heating for only 2 h (Scheme 1).

Scheme 1. Preparation of 3-(2-hydroxyethyl)-2-methylbenzothiazolium bromide 3 by quaternization with 2-bromoethanol 2.

The structure of 3-(2-hydroxyethyl)-2-methylbenzothiazolium bromide was confirmed by NMR spectra (See Supplementary Materials).

2. Experimental Section

2.1. Materials

Unless otherwise stated, all reagents and solvents used in the synthesis and analysis were obtained from Sigma-Aldrich (St. Louis, MO, USA), Alfa-Aesar (Haverhill, MA, USA), as commercial products of analytical grade, and used without further purification.

2.2. Instrumentation

¹H-NMR spectrum were recorded on a Bruker Avance III 500 MHz (Rheinstetten, Germany) using DMSO-d₆ at room temperature. Chemical shifts (δ) are reported in ppm and referenced indirectly to the corresponding shift of the deuterated solvent peak. The melting point temperatures were determined on a Kofler bench apparatus (DDR, Berlin, Germany) and are uncorrected.

2.3. Experimental Procedure for the Preparation of 3-(2-hydroxyethyl)-2-methylbenzothiazolium Bromid

А 250 mL Erlenmeyer flask was charged with 2-methylbenzothiazole 1 (12.70 mL, 0.1 mol), 2-bromoethanol 2 (10.00 mL, 0.14 mol), and 15 mL ethoxyethanol. The reaction mixture was heated under reflux and stirred for 120 min. The reaction mixture was cooled down to room temperature and left at room temperature for 24 h. On the next day the precipitate of 3 was filtered off and air dried. The compound was recrystallized from methanol/ethylacetate with charcoal. The crude yield of 3 was 80%. The pure product for 3-(2-hydroxy-ethyl)-2-methylbenzothiazolium bromide had a melting point 166–168 °C (methanol/ethyl acetate)— lit. m.p.178 °C [2].

3-(2-Hydroxyethyl)-2-methylbenzothiazolium Bromide 5 ¹H-NMR (DMSO-d₆) δ (ppm): 3.24 (s, 3H, CH₃); 3.89 (t, 2H, CH₂OH, J = 5.0 Hz); 4.87 (t, 2H, CH₂N, J = 5.0 Hz); 5.23 (br.s, 1H, OH); 7.80 (t, 1H, H-Ph, J = 7.6 Hz); 7.87 (t, 1H, H-Ph, J = 7.6 Hz); 8.34 (d, 1H, H-Ph, J = 8.3 Hz); 8.47 (d, 1H, H-Ph, J = 8.3 Hz); ¹³C-NMR (DMSO-d₆) δ (ppm): 17.41 (1C, CH₃); 51.99 (1C, CH₂N); 58.53 (1C, CH₂OH); 117.13 (1C, Ph); 124.61 (1C, Ph); 128.03 (1C, Ph); 129.01 (1C, Ph); 129.22 (1C, Ph); 141.11 (1C, Ph); 178.03 (1C, NCS).

Supplementary Materials

The following are available online at www.mdpi.com/1422-8599/2016/4/M920.

Supplementary File 1Supplementary File 2Supplementary File 3

Acknowledgments

All sources of funding of the study should be disclosed. Please clearly indicate grants that you have received in support of your research work. Clearly state if you received funds for covering the costs to publish in open access.

Author Contributions

The listed authors contributed to this work as follows: T.D. contributed to the synthetic approach and together with N.G. carried out the described method. N.G. recrystallized the compounds, S.M. and A.A. prepared the manuscript. N.B. acquired and assigned the 1H- and 13C-NMR spectra. All authors read and approve the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Scheme 1. Preparation of 3-(2-hydroxyethyl)-2-methylbenzothiazolium bromide 3 by quaternization with 2-bromoethanol 2.

Molbank 2016 m920 sch001

References

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3. Wang, H.-M. Confirmation of structure of 2-substituted benzothiazole derivatives. Huaxue Yu Nianhe 2007, 29, 296–301.

4. Ye, C.-P.; Ren, J.-Q.; Ge, H.-Q.; Lu, X.-H. Synthesis of 2-substituted benzothiazoline derivatives. Hecheng Huaxue 2005, 13, 206–207.

5. Hyodo, Y.; Yagi, S.; Kitayama, H.; Nakazumi, H. Synthesis of polymer liquid crystals containing squarylium dyes. Shikizai Kyokaishi 2003, 76, 3–8.

6. Li, Z.G.; Wu, C.H.; Xu, S. Preparation of squaraine chemical sensor for colorimetric identification of Fe and Cu ions. CN Patent 103172590, 26 June 2013.

7. Inagaki, Y. Methine compounds and manufacture thereof. JP Patent 08043979, 16 February 1996.

8. Gupta, R.; Lee, S.Y.; Shen, G.-Y.; Szydlo, G.S.; Deka, C. Dyes and methods of detection of nucleic acid in immature red blood cells. U.S. Patent 20020037589, 28 March 2002.